Immunoreactivity for calretinin and keratins in desmoid fibromatosis and other myofibroblastic tumors: a diagnostic pitfall.

Immunoreactivity for calretinin and keratins in desmoid fibromatosis and other myofibroblastic tumors: a diagnostic pitfall.
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DOI:
10.1097/pas.0b013e3182556def
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发表时间:
2012-09
期刊:
The American journal of surgical pathology
影响因子:
--
通讯作者:
Miettinen M
Miettinen M
中科院分区:
其他
文献类型:
--
作者:
Barak S;Wang Z;Miettinen M

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Calretinin 是钙调蛋白超家族的一种细胞内钙结合 EF 手蛋白。它在多种细胞功能中发挥作用,包括信息靶向和细胞内钙信号传导。它在间皮、肥大细胞、一些神经细胞和脂肪细胞等中表达。由于其对间皮肿瘤的相对特异性,钙结合蛋白被广泛用作恶性间皮瘤的主要免疫组织化学标记物之一,并用于区分其与腺癌。基于我们对硬纤维瘤病中钙结合蛋白免疫反应性的零星观察,我们系统地评估了 268 例成纤维细胞/肌纤维母细胞肿瘤中的钙结合蛋白、角蛋白混合物 (AE1/AE3) 和 WT1 免疫反应性。在 75% (44/58) 硬纤维瘤病、50% (21/42) 增殖性筋膜炎、23% (8/35) 结节性筋膜炎、33% (13/40) 良性纤维组织细胞瘤、35% (22/62) 恶性纤维组织细胞瘤和 13% 中观察到钙结合蛋白(4/31) 存在于孤立性纤维性肿瘤中,但存在于不同部位的正常结缔组织成纤维细胞中。角蛋白 AE1/AE3 免疫反应性也常见 (6/13) 存在于增殖性筋膜炎的大神经节样细胞中,有时也存在于结节性筋膜炎 (3/35)、孤立性纤维瘤 (3/27) 和恶性纤维组织细胞瘤 (9/62) 中。在肌纤维母细胞肿瘤中未检测到 WT1 或角蛋白 5 阳性的核免疫反应性。基于这些观察,可以得出结论,钙结合蛋白和局灶角蛋白免疫反应性在良性和恶性成纤维细胞和肌纤维母细胞病变中相当常见。硬纤维和结节性筋膜炎中的钙结合蛋白阳性和角蛋白阳性梭形细胞或增殖性筋膜炎中的钙结合蛋白阳性神经节样细胞不应与上皮样或肉瘤样间皮瘤的成分相混淆。通过仔细观察形态、角蛋白表达的定量差异以及使用角蛋白 5 和 WT1 等其他免疫组织化学标记来验证间皮瘤典型的真实上皮和间皮分化,可以避免这些诊断陷阱。
Calretinin is an intracellular calcium-binding EF-hand protein of the calmodulin superfamily. It plays a role in diverse cellular functions, including message targeting and intracellular calcium signaling. It is expressed in the mesothelium, mast cells, some neural cells, and fat cells, among others. Because of its relative specificity for mesothelial neoplasms, calretinin is widely used as one of the primary immunohistochemical markers for malignant mesothelioma and in differentiating it from adenocarcinoma. On the basis of our sporadic observation on calretinin immunoreactivity in desmoid fibromatosis, we systematically evaluated calretinin, keratin cocktail (AE1/AE3), and WT1 immunoreactivity in 268 fibroblastic/myofibroblastic neoplasms. Calretinin was observed in 75% (44/58) of desmoid fibromatosis, 50% (21/42) of proliferative fasciitis, 23% (8/35) of nodular fasciitis, 33% (13/40) of benign fibrous histiocytoma, 35% (22/62) of malignant fibrous histiocytoma, and 13% (4/31) of solitary fibrous tumors but not in normal connective tissue fibroblasts at various sites. Keratin AE1/AE3 immunoreactivity was also commonly (6/13) present in the large ganglion-like cells of proliferative fasciitis and sometimes in nodular fasciitis (3/35), solitary fibrous tumor (3/27), and malignant fibrous histiocytoma (9/62). Nuclear immunoreactivity for WT1 or keratin 5 positivity was not detected in myofibroblastic tumors. On the basis of these observations, it can be concluded that calretinin and focal keratin immunoreactivity is fairly common in benign and malignant fibroblastic and myofibroblastic lesions. Calretinin-positive and keratin-positive spindle cells in desmoid and nodular fasciitis or calretinin-positive ganglion-like cells in proliferative fasciitis should not be confused with elements of epithelioid or sarcomatoid mesothelioma. These diagnostic pitfalls can be avoided with careful observation of morphology, quantitative differences in keratin expression, and use of additional immunohistochemical markers such keratin 5 and WT1 to verify true epithelial and mesothelial differentiation typical of mesothelioma.